title: Nuclear phosphoinositides and their impact on nuclear functions.
abstract: Polyphosphoinositides (PPIn) are important lipid molecules whose levels are de-regulated in human diseases such as cancer, neurodegenerative disorders and metabolic syndromes. PPIn are synthesized and degraded by an array of kinases, phosphatases and lipases which are localized to various subcellular compartments and are subject to regulation in response to both extra- and intracellular cues. Changes in the activities of enzymes that metabolize PPIn lead to changes in the profiles of PPIn in various subcellular compartments. Understanding how subcellular PPIn are regulated and how they affect downstream signaling is critical to understanding their roles in human diseases. PPIn are present in the nucleus, and their levels are changed in response to various stimuli, suggesting that they may serve to regulate specific nuclear functions. However, the lack of nuclear downstream targets has hindered the definition of which pathways nuclear PPIn affect. Over recent years, targeted and global proteomic studies have identified a plethora of potential PPIn-interacting proteins involved in many aspects of transcription, chromatin remodelling and mRNA maturation, suggesting that PPIn signalling within the nucleus represents a largely unexplored novel layer of complexity in the regulation of nuclear functions.
authors.affiliation: Cancer Research UK Inositide Laboratory, Paterson Institute for Cancer Research, Manchester, UK.
authors.forename: Zahid H
authors.initials: ZH
authors.lastname: Shah
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: Lilly
authors.initials: L
authors.lastname: Sommer
authors.forename: Rebecca
authors.initials: R
authors.lastname: Foulger
authors.forename: Yvette
authors.initials: Y
authors.lastname: Bultsma
authors.forename: Clive
authors.initials: C
authors.lastname: D'Santos
authors.forename: Nullin
authors.initials: N
authors.lastname: Divecha
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010716:Phosphatidylinositols
keywords: PHD finger; chromatin; epigenetic; inositol phosphate; lipid kinase; nuclear; phosphoinositides; signalling; splicing; transcription